This invention relates to a method for producing pharmaceuticals in a solid form of application that contain plant extracts, in particular, St. John""s wort extract.
The advantage of solid forms of pharmaceuticals such as tablets or capsules as compared to liquid forms of application is that they act in more downstream sections of the intestinal duct. This facilitates a more controlled release of the active ingredients and therefore better therapeutic control. The doctor can exactly dose each individual dose administered to treat a patient as required. In addition, solid pharmaceuticals are extremely stable and easily packaged, stored and transported.
An unsatisfactory aspect about administering tablets or capsules containing plant extracts, however, is that they are characterized by a large portion of adjuvants combined with relatively small portions of pharmaceutically active plant extracts so that their absorption and active agent concentrations at the absorption site are rather low. Furthermore, these tablets are comparatively large which makes it difficult for patients to swallow them.
DE 197 00 788 A1 disclosed a pharmaceutical based on St. John""s wort extract that can be administered orally in dried form as a powder, granulate, capsule, or tablet. This document, however, does not reveal any engineering instructions as to how a tablet that is highly enriched with plant extract should be manufactured.
DE 196 39 375 A1 describes a dry mistletoe extract that is to be used as a powder or granulate in a capsule or tablet, or as a liquid. In particular, this invention suggests oral administration of a granulate containing calcium carbonate or saccharide.
A similar form of application is known from DE 196 27 376 A1 for a pharmaceutical based on an artichoke extract.
The pharmaceuticals mentioned above all share the disadvantage that they do not represent forms of application highly enriched with dried plant extract. This means that multiple tablets or a tablet so big that it cannot be swallowed would have to be administered if the dosage of the pharmaceutical is sufficiently high.
DE 36 16 054 A1 claims a homeopathic pharmaceutical. To produce this pharmaceutical, triturations of pig""s bone marrow, pig""s articular cartilage, gelatin and harpagophytins as well as an extremely high portion of adjuvants are granulated through a sieve. The granulate is cross-linked with more adjuvants and pressed into tablets. As this product has such a high portion of adjuvants, this method of manufacturing tablets from granulate cannot be used for tablets from plant extracts sized for oral application, which means tablets that are as low in adjuvants and as high in dried extract as possible.
A pharmaceutical preparation of extracts from various drugs known from DE 33 28 262 C 2 can be administered as a liquid or as a dry extract in the form of a powder, granulate, tablet, or capsule. In one of its embodiments, the powdered dry extract is mixed with lactose and magnesium stearate and pressed into tablets that are later granulated to yield the ready-for-use pharmaceutical preparation. In a second embodiment, the powdered dry extract is mixed with cellulose and magnesium stearate and immediately pressed into tablets. Although this patent describes solid forms of application that have a high portion of plant extracts, a tablet pressed in this way from a dry extract does not guarantee compliance with the parameters a pharmaceutical calls for, such as disintegration time and moisture protection.
JP 78 13 347 and JP 77 102 4416 each describe the manufacture of granulates produced from plant extracts by adding various adjuvants without specifically claiming conditions required for the industrial production of tablets containing a high portion of dry extract and meeting other requirements a conventional pharmaceutical would have to meet.
It is therefore the problem of this invention to propose a method for producing ready-made pharmaceuticals in a solid form of application whose active ingredient is a plant extract, and thereby to provide a galenically stable, highly effective pharmaceutical containing a large dose of extract in a comparatively small tablet that is easily dissolved and absorbed at the place of release.
This problem is solved according to the invention by a method comprising the characteristics described in claim 1.
In other words, it is the concept of the invention to compact a dry extract into granulate particles screened to a uniform size and to mask these particles in a mixing process with three layers of titanium dioxide, talc, and highly dispersed silicon dioxide. These granulate particlesxe2x80x94compacted and masked with other adjuvants as may be requiredxe2x80x94are then further processed in the usual way to become tablets or capsules.
The combination of a compacting step, a screening to uniform grain size step, and a masking step as described yields a raw material that has good flow characteristics, an extremely high extract content, requires an accordingly smaller portion of adjuvants, and is therefore suited for the industrial manufacture of tablets and capsules. As the extract portion in the masked compacted matter is at least 65 percent by weight, a highly effective pharmaceutical based on plant extracts can be provided in typical tablet size. The adjuvants applied in the defined order when masking the granulate particles do not conflict with the efficacy of the pharmaceutical as the outer coat of highly disperse silicon dioxide prevents the granulate particles from melting into one another at their outer surfaces so that they disintegrate fast after intake and unfold their full efficacy.
In the three-step masking process, the titanium dioxide, which preferably is applied first, covers all surface areas of the granulate particles and provides moisture protection for the typically hygroscopic extract. The talc applied subsequently to the titanium dioxide coat fills any remaining spaces of the granulate surface to yield a smooth and continuous surface. Finally, the highly dispersed silicon dioxide as the outer coat acts as a separating layer between granulate particles in a pressed tablet. The granulate particles masked in this way are also characterized by good flowability, which is advantageous for further processing.